Methods of evaluating and making biologics

Abstract

Methods of making and evaluating biologic therapeutic products are disclosed.

1 .- 147 . (canceled) 
     
     
         148 . A method comprising:
 acquiring, from a test protein preparation, a value for each of a plurality of parameters,
 wherein the test protein is not approved under a biologics license application (BLA) or a supplemental BLA, 
 wherein the plurality of parameters includes two or more determinative parameters, 
 wherein a signature consists of the two or more determinative parameters and values for a target protein for the determinative parameters, and wherein the signature distinguishes the target protein from a plurality of antibody or Fc-containing non-target proteins; 
   manufacturing a protein drug product by formulating at least a portion of the test protein preparation into the protein drug product if all of the values acquired from the test glycoprotein preparation for the determinative parameters in the signature are indistinguishable from the values in the signature; and   discarding the test protein preparation if any one of the values acquired from the test protein preparation for the determinative parameters in the signature is distinguishable from the values in the signature;   wherein the target protein: (i) has an amino acid sequence that is at least 95% identical to the test protein amino acid sequence, or (ii) has an amino acid sequence that differs by less than 10 amino acids from the test protein amino acid sequence, and wherein the target protein is approved under a BLA, a supplemental BLA, or an equivalent thereof.   
     
     
         149 . The method of  claim 148 , wherein at least one value acquired from the test protein preparation for each determinative parameter in the signature is directly acquired or is acquired by performing an analytical analysis on said test protein preparation. 
     
     
         150 . The method of  claim 148 , wherein formulating comprises combining the test protein preparation with a second component. 
     
     
         151 . The method of  claim 148 , wherein a value for a target protein for a determinative parameter:
 (i) is a value for the determinative parameter in 1 or more, commercially available samples, or batches, of the target protein, or   (ii) is an average value or a range for the values for the determinative parameter in 2 or more commercially available samples or batches of the target protein.   
     
     
         152 . The method of  claim 148 , wherein a value for a target protein for a determinative parameter in the signature is an average value or a range of values for the determinative parameter determined from 2 or more samples or batches of the target protein; and
 the method further comprises comparing the average value or the range of values from the target protein for the determinative parameter with the value acquired from the test protein preparation for the determinative parameter.   
     
     
         153 . The method of  claim 148 , wherein the signature includes at least 4 determinative parameters. 
     
     
         154 . The method of  claim 148 , wherein the values for the plurality of parameters are acquired from one sample or batch of the test protein preparation. 
     
     
         155 . The method of  claim 148 , wherein the values for the plurality of parameters are acquired from 2 or more samples or batches of the test protein preparation. 
     
     
         156 . The method of  claim 148 , wherein the test protein is a glycoprotein. 
     
     
         157 . The method of  claim 148 , wherein the test protein is an antibody. 
     
     
         158 . The method of  claim 148 , wherein the test protein is a glycoprotein, and the signature comprises at least 2 of the following: HM3 glycan, HM5 glycan, a bisecting glycan, C-terminal amino acid, sialylated glycan, a G0F glycan, a G1F glycan, a G2F glycan, or terminal galactose-alpha-1-3-galactose. 
     
     
         159 . The method of  claim 148 , further comprising:
 providing a unique seriousness value for at least one determinative parameter in the signature, wherein said seriousness value is a function of a risk associated with variation of the at least one determinative parameter; and   generating a sameness/identity value for said test protein preparation based on the plurality of comparisons and seriousness values.   
     
     
         160 . The method of  claim 159 , wherein said seriousness value is a function of the level of terminal galactose-alpha-1-3-galactose in said test protein preparation. 
     
     
         161 . The method of  claim 159 , wherein the seriousness values for at least 2 parameters associated with said test protein preparation are provided. 
     
     
         162 . The method of  claim 159 , wherein said risk is a risk associated with safety or efficacy. 
     
     
         163 . The method of  claim 148 , wherein the plurality of parameters comprises at least one non-determinative test protein parameter that does not distinguish the target protein from at least one of the plurality of antibody or Fc-containing non-target proteins. 
     
     
         164 . The method of  claim 150 , wherein the second component is an excipient or buffer. 
     
     
         165 . The method of  claim 157 , wherein the test antibody is a CDR-grafted antibody, a humanized antibody, a human antibody, or a glycosylated therapeutic antibody. 
     
     
         166 . The method of  claim 148 , wherein the target protein has an amino acid sequence that is 100% identical to the test protein amino acid sequence.